Antimicrobial drug resistance has emerged rapidly and thwarted most treatment options, leading to prolonged illness, disability, and death. Despite considerable efforts to develop new antimicrobial drugs, many bacterial infections remain difficult to treat due to acquired drug resistance. Compared to small molecular antibiotics designed to interrupt the bacterial intracellular biochemical processes, antimicrobial polymers target the disruption of membrane integrity, offering a promising strategy to overcome drug resistance. Bacteria have little chance of developing a resistance mechanism against the physical disruption, which often leads to cell death.
The design principle of antimicrobial polymers has been focused primarily on balancing positive charges with the hydrophobicity in the pendant side chains in order to achieve selective disruption of the bacterial membrane over the mammalian cell membranes. By polymerizing various monomers containing positively charged hydrophobic side chains, many polymers with different functionalities and architectures have been developed and demonstrated for antimicrobial activities against a broad spectrum of bacterial species. Although current synthetic approaches have proven capable of developing highly selective antimicrobial polymers, a simple synthetic method for developing antimicrobial polymers with improved biocompatibility, selectivity, and specificity is needed.
Similar to facially structured host defense antimicrobial peptides (AMPs), antimicrobial polymers are attracted by the envelope components, transferred to the bacterial membrane, and adopt amphiphilic conformations necessary for disrupting the membrane. Recent molecular dynamic simulations suggest that the randomly distributed and oriented polymer side chains are reorganized into ordered amphiphilic chain architectures upon interacting with the negatively charged bacterial membrane. To this end, the design and development of polymers that favor the membrane disruption processes by compensating for the thermodynamic entropy loss upon forming ordered structures with enthalpy gains due to ionic, hydrophobic, and hydrogen-bonding (H-bonding) interactions are desired.